This proposal requests support for a Keystone Symposia meeting entitled ApoE, Alzheimer's and Lipoprotein Biology, organized by Joachim Herz, David M. Holtzman and Eric M. Parker, which will be held in Keystone, Colorado from February 26 - March 2, 2012. Apolipoprotein E4 (ApoE4) genotype is the primary risk factor for late-onset Alzheimer's disease. Approximately one fifth of the human population are ApoE4 carriers yet, more than 17 years after its discovery, the molecular basis by which this common allele causes neurodegeneration is still not understood. One major reason is the lack of effective communication between lipid researchers, who have investigated the role of ApoE as a plasma lipid transport protein, and neuroscientists, who are unfamiliar with the complex biochemistry of lipid metabolism and the cell biology of ApoE receptors. This is confounded by the methodological difficulty of studying lipid metabolism and lipoprotein transport in the brain and the paucity of pioneering work tackling this problem. Yet, the solution to one of the most pressing socioeconomic problem of our times, the looming Alzheimer's disease epidemic, depends on our ability to dissect and understand the molecular mechanism by which ApoE4 is causing this disease. The purpose of this highly interdisciplinary meeting on ApoE, Alzheimer's and Lipoprotein Biology is to bring together a critical mass of experts with complementary expertise from these different fields, but who do not normally collaborate or attend the same conferences. In this manner, we envisage this meeting serving as the main catalyst for communication and collaboration between lipid and lipoprotein researchers, neurogeneticists, cell biologists and synaptic neurophysiologists. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies, which will share opening Keynote addresses and a fourth day of sessions with this meeting. PUBLIC HEALTH RELEVANCE: Approximately one fifth of the human population is ApoE4 carriers - having a genotype that is a primary risk factor for late-onset Alzheimer's disease (AD). Yet, more than 17 years after its discovery, the molecular basis by which this common allele causes neurodegeneration is still not well understood. Scientists working at the cutting edge of lipoprotein metabolism, cell biology, neurophysiology, neuroimaging, drug design and industrial pharmaceutical research will come together at the 2012 Keystone Symposia meeting on ApoE, Alzheimer's and Lipoprotein Biology to critically examine the role ApoE plays in AD pathogenesis and to apply this understanding to developing treatments for AD.